Abstract：
Sepsis accompanied by myocardial injury is an important cause of multiple organ dysfunction, and its underlying molecular mechanism is not fully clear. Although diverse effects of fibroblast growth factor (FGF) in heart have been discovered till now, the specific role of FGF5 in heart remains unclear. Therefore, our study aims to explore the possible impacts of FGF5 on sepsis-induced cardiac injury. Sepsis-induced cardiac injury was established through administration of lipopolysaccharide (LPS). The expression level of FGF5 in sepsis heart was decreased, and injection of FGF5-overexpressing adenovirus attenuated cardiac injury reflected by echocardiographic and pathological findings. Besides, FGF5 overexpression, not only in vivo heart but also in vitro cardiomyocytes, reduced the levels of oxidative stress and pyroptosis resulted from LPS. In addition, overexpression of FGF5 reduced LPS-activated the levels of phosphorylated CaMKII (p-CaMKII), p-NFκB, NLRP3, caspase-1, IL-1β and IL-18. Furthermore, KN93, the inhibitor of CaMKII, exerted the similarly protective effects on LPS-induced pyroptosis. In summary, our study implied the beneficial effects of FGF5 on LPS-induced cardiac injury, which was at least partially attributed to the inhibition of CaMKII-mediated pyroptotic signaling.
摘要：
脓毒症合并心肌损伤是导致多器官功能障碍的重要原因,其潜在的分子机制尚不完全清楚。尽管目前已发现成纤维细胞生长因子(FGF)在心脏中的多种作用,FGF5在心脏中的具体作用尚不清楚.因此,本研究旨在探讨FGF5对脓毒症心脏损伤的可能影响.通过给予脂多糖(LPS)建立脓毒症诱导的心脏损伤。FGF5在脓毒症心脏中的表达程度降低，注射过表达FGF5的腺病毒可减轻超声心动图和病理结果所反映的心脏损伤。此外,FGF5过表达，不仅在体内心脏，而且在体外心肌细胞，降低了LPS导致的氧化应激和焦亡水平。此外,FGF5的过表达降低了LPS激活的磷酸化CaMKII（p-CaMKII）的水平，p-NFκB,NLRP3、caspase-1、IL-1β和IL-18。此外，KN93，CaMKII的抑制剂，对LPS诱导的焦亡具有类似的保护作用。总之,我们的研究暗示FGF5对LPS诱导的心脏损伤的有益作用，这至少部分归因于CaMKII介导的焦转信号传导的抑制。
